From bench to bedside a comprehensive review of pancreatic cancer immunotherapy

Kunk, Paul R.; Bauer, Todd W.; Slingluff, Craig L.; Rahma, Osama E.

doi:10.1186/s40425-016-0119-z

Table 2 Completed immunotherapy clinical trials

From: From bench to bedside a comprehensive review of pancreatic cancer immunotherapy

Treatment type	Target	N	Additional therapy	Cancer stage	Immunologic response	Clinical outcome	Ref
Peptide vaccines	CEA	23	None	Resected or Metastatic	↑ IFN-γ T cell response by ELISPOT with increasing vaccine dose	37 % survival at 32 months	[77]
	CEA + MUC1	20	None	Metastatic	NR	mOS of 7.3 ms	[78]
	Gastrin 17	154	None	Metastatic	74 % + ELISA	↑OS by 54 % vs placebo (p = 0.03)	[51]
	Gastrin 17	383	None	Metastatic	Correlation between anti-gastrin17 titers and OS	No benefit	[53]
	Gastrin 17	30	None	Metastatic	67 % + ELISA	↑OS (4 to 7.2 ms if + IR (p < 0.01)	[52]
	GVAX + Mesothelin	90	Cyclophosphamide	Metastatic	NR	↑OS (4 to 6.2 ms)	[63]
	Hedgehog	59	Gemcitabine	Metastatic	NR	mOS 10 ms	[79]
	KRAS	23	None	Resected	85 % + DTH	10 year OS of 20 %	[56]
	KRAS	48	GM-CSF	Resected(10) and Metastatic (38)	58 % + DTH	↑OS (2 to 5.4 ms if + IR (p = 0.0002)	[54]
	KRAS	24	GM-CSF	Resected	11 % + DTH	mOS 20.3 ms	[55]
	KRAS	39	Gemcitabine	Resected	47 % + ELISpot	↑OS by 21.7 wks if + IR (p < 0.01)	[57]
	MUC1	16	SB-AS adjuvant	Resected	31 % + DHT	No benefit	[42]
	MUC1	6	Incomplete Freund's	Metastatic	17 % + ELISA	No benefit	[41]
	Telomerase	1062	Gemcitabine	Metastatic	NR	No benefit	[47]
	Telomerase	520	Gemcitabine	Metastatic	NR	No benefit	[48]
	Telomerase	48	GM-CSF	Metastatic	63 % + DHT	mOS of 4.3 ms if + IR (p < 0.01)	[50]
	Telomerase	178	Gemcitabine	Metastatic	NR	No benefit	[49]
	Trop-2	7	None	Metastatic	NR	No benefit	[80]
	VEGF	607	Erlotinib + Gemcitabine	Metastatic	NR	No benefit	[44]
	VEGF	535	Gemcitabine	Unresectable	NR	No benefit alone	[46]
	VEGF	150	Gemcitabine	Unresectable	NR	No benefit	[46]
	Wilm's Tumor gene-1	32	Gemcitabine	Unresectable	58 % + DTH	↑mOS by 7 ms if DHT + (p < 0.01)	[81]
Autologous: DC	MUC-1	49	Gemcitabine	Metastatic	↓65 % T-regs	2 CR, 5 PR ,10 SD	[59]
	MUC1	17	None	Resected and Unresectable	NR	mOS of 9 ms	[82]
	MUC-1	20	none	Metastatic	Correlation between CD38+ cells and OS	1 pt had remission of lung mets, 5 had stable disease. mOS 9.8 mos	[58]
	MUC-1	10	None	Resected	No difference	30 % OS 4 years	[83]
	MUC-1	2	None	Metastatic	↑117 % CD8+ MUC-1 specific cells	No benefit	[84]
	Wilm's Tumor gene-1	10	Gemcitabine	Metastatic	57 % + DTH	↑OS if + DTH	[85]
Allogeneic	GM-CSF	60	5-FU	Resected	↑ mesothelin + ELISPOT	↑OS (53 % to 76 % if + IR)	[61]
	GM-CSF	14	Adjuvant CRT	Resected	21 % + DTH	DFS of 25 ms if + R	[60]
	GM-CSF	30	Cyclophosphamide	Metastatic	↑Mesothelin ELISPOT	No benefit	[62]
Adoptive cell transfer	Mesothelin	6	None	Metastatic	NR	33 % with stable disease	[65]
	MUC1	28	None	Resected (20) and Unresectable (8)	↑10 % effector T-cells , ↓5.7 % Tregs	mOS 5 ms in unresectable, 19 % 3 year OS in resectable	[64]
	MUC1	20	None	Unresected	↑CD8+ T-cells	mOS 9.8 ms, 1 year OS 20 %	[58]
Immune checkpoint inhibitor	CD40	21	Gemcitabine	Unresected (7) and Metastatic (20)	N/A	↑mOS by 1.7 ms vs gemcitabine alone, 1 patient had complete resolution of hepatic metasteses	[68]
	CTLA-4	30	GVAX	Unresectable or metastatic	N/A	↑1 year OS by 20 % compared to GVAX alone	[75]
	CTLA-4	27	none	Unresected (7) and Metastatic (20)	N/A	1 patient delayed regression of hepatic metasteses	[70]
	PD-L1	14	none	Metastatic	N/A	No benefit	[69]

↑ increase, ↓ decrease, CR complete response, CRT chemoradiation, CTLA-4 Cytotoxic T-lymphocyte associated protein-4, DC dendritic cell, DTH delayed typed hypersensitivity, GM-CSF granulocyte macrophage colony stimulating factor, MDSC myeloid derived suppressor cell, mOS median overall survival, Ms months, N/A not applicable, NK natural killer cell, NR not reported, OS overall survival, PD-L1, programmed cell death ligand-1, PR partial response, R response, SD stable disease, TAM tumor associated macrophages, Wk weeks

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